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A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea.

Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rosen PJ, Rumi E, Gattoni E, Pieri L, Guglielmelli P, Elena C, He S, Contel N, Mookerjee B, Sandor V, Cazzola M, Kantarjian HM, Barbui T, Vannucchi AM - Cancer (2014)

Bottom Line: Ruxolitinib treatment also reduced elevated levels of inflammatory cytokines and granulocyte activation.Thrombocytopenia and anemia were the most common adverse events.Thrombocytopenia of grade 3 or anemia of grade 3 (according to National Cancer Institute Common Terminology Criteria for Adverse Events,version 3.0) occurred in 3 patients each (9%) (1 patient had both) and were managed with dose modification.Ruxolitinib was generally well tolerated and provided rapid and durable clinical benefits in patients with advanced PV who were refractory or intolerant to hydroxyurea.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with somatic gain-of-function mutations of Janus kinase-2 (JAK2). Therapeutic options are limited in patients with advanced disease. Ruxolitinib, an oral JAK1/JAK2 inhibitor, is active in preclinical models of PV. The long-term efficacy and safety of ruxolitinib in patients with advanced PV who are refractory or intolerant to hydroxyurea were studied in a phase 2 trial.

Methods: Response was assessed using modified European LeukemiaNet criteria, which included a reduction in hematocrit to <45% without phlebotomy, resolution of palpable splenomegaly, normalization of white blood cell and platelet counts, and reduction in PV-associated symptoms.

Results: Thirty-four patients received ruxolitinib for a median of 152 weeks (range, 31 weeks-177 weeks) or 35.0 months (range, 7.1 months-40.7 months). Hematocrit <45% without phlebotomy was achieved in 97% of patients by week 24.Only 1 patient required a phlebotomy after week 4. Among patients with palpable splenomegaly at baseline, 44% and 63%, respectively, achieved nonpalpable spleen measurements at weeks 24 and 144. Clinically meaningful improvements in pruritus, night sweats, and bone pain were observed within 4 weeks of the initiation of therapy and maintained with continued treatment. Ruxolitinib treatment also reduced elevated levels of inflammatory cytokines and granulocyte activation. Thrombocytopenia and anemia were the most common adverse events.Thrombocytopenia of grade 3 or anemia of grade 3 (according to National Cancer Institute Common Terminology Criteria for Adverse Events,version 3.0) occurred in 3 patients each (9%) (1 patient had both) and were managed with dose modification.

Conclusions: Ruxolitinib was generally well tolerated and provided rapid and durable clinical benefits in patients with advanced PV who were refractory or intolerant to hydroxyurea.

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Related in: MedlinePlus

Reduction in polycythemia vera-associated symptoms with ruxolitinib therapy is shown. The percentages of patients who were treated with ruxolitinib and who achieved a ≥ 50% reduction and a 100% reduction in pruritus, night sweats, and bone pain over the previous week among patients with symptom scores > 2 at baseline are shown. A 100% reduction corresponds to a score of 0 for individual symptoms.
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fig03: Reduction in polycythemia vera-associated symptoms with ruxolitinib therapy is shown. The percentages of patients who were treated with ruxolitinib and who achieved a ≥ 50% reduction and a 100% reduction in pruritus, night sweats, and bone pain over the previous week among patients with symptom scores > 2 at baseline are shown. A 100% reduction corresponds to a score of 0 for individual symptoms.

Mentions: Reduction in palpable spleen length was rapid. Among patients with palpable splenomegaly with a recorded spleen measurement at baseline, 70% achieved a ≥ 50% reduction in palpable spleen at week 24. In addition, 44% of patients with palpable splenomegaly at baseline reduced their spleen size to become nonpalpable at week 24. By week 144, 64% of patients had achieved a ≥ 50% reduction in palpable spleen length and 63% had reduced their spleen size to become nonpalpable (Fig. 2d). Clinically meaningful improvements in pruritus, night sweats, and bone pain were observed within 4 weeks of the initiation of therapy and were maintained through week 144 (Fig. 3).


A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea.

Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rosen PJ, Rumi E, Gattoni E, Pieri L, Guglielmelli P, Elena C, He S, Contel N, Mookerjee B, Sandor V, Cazzola M, Kantarjian HM, Barbui T, Vannucchi AM - Cancer (2014)

Reduction in polycythemia vera-associated symptoms with ruxolitinib therapy is shown. The percentages of patients who were treated with ruxolitinib and who achieved a ≥ 50% reduction and a 100% reduction in pruritus, night sweats, and bone pain over the previous week among patients with symptom scores > 2 at baseline are shown. A 100% reduction corresponds to a score of 0 for individual symptoms.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231215&req=5

fig03: Reduction in polycythemia vera-associated symptoms with ruxolitinib therapy is shown. The percentages of patients who were treated with ruxolitinib and who achieved a ≥ 50% reduction and a 100% reduction in pruritus, night sweats, and bone pain over the previous week among patients with symptom scores > 2 at baseline are shown. A 100% reduction corresponds to a score of 0 for individual symptoms.
Mentions: Reduction in palpable spleen length was rapid. Among patients with palpable splenomegaly with a recorded spleen measurement at baseline, 70% achieved a ≥ 50% reduction in palpable spleen at week 24. In addition, 44% of patients with palpable splenomegaly at baseline reduced their spleen size to become nonpalpable at week 24. By week 144, 64% of patients had achieved a ≥ 50% reduction in palpable spleen length and 63% had reduced their spleen size to become nonpalpable (Fig. 2d). Clinically meaningful improvements in pruritus, night sweats, and bone pain were observed within 4 weeks of the initiation of therapy and were maintained through week 144 (Fig. 3).

Bottom Line: Ruxolitinib treatment also reduced elevated levels of inflammatory cytokines and granulocyte activation.Thrombocytopenia and anemia were the most common adverse events.Thrombocytopenia of grade 3 or anemia of grade 3 (according to National Cancer Institute Common Terminology Criteria for Adverse Events,version 3.0) occurred in 3 patients each (9%) (1 patient had both) and were managed with dose modification.Ruxolitinib was generally well tolerated and provided rapid and durable clinical benefits in patients with advanced PV who were refractory or intolerant to hydroxyurea.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with somatic gain-of-function mutations of Janus kinase-2 (JAK2). Therapeutic options are limited in patients with advanced disease. Ruxolitinib, an oral JAK1/JAK2 inhibitor, is active in preclinical models of PV. The long-term efficacy and safety of ruxolitinib in patients with advanced PV who are refractory or intolerant to hydroxyurea were studied in a phase 2 trial.

Methods: Response was assessed using modified European LeukemiaNet criteria, which included a reduction in hematocrit to <45% without phlebotomy, resolution of palpable splenomegaly, normalization of white blood cell and platelet counts, and reduction in PV-associated symptoms.

Results: Thirty-four patients received ruxolitinib for a median of 152 weeks (range, 31 weeks-177 weeks) or 35.0 months (range, 7.1 months-40.7 months). Hematocrit <45% without phlebotomy was achieved in 97% of patients by week 24.Only 1 patient required a phlebotomy after week 4. Among patients with palpable splenomegaly at baseline, 44% and 63%, respectively, achieved nonpalpable spleen measurements at weeks 24 and 144. Clinically meaningful improvements in pruritus, night sweats, and bone pain were observed within 4 weeks of the initiation of therapy and maintained with continued treatment. Ruxolitinib treatment also reduced elevated levels of inflammatory cytokines and granulocyte activation. Thrombocytopenia and anemia were the most common adverse events.Thrombocytopenia of grade 3 or anemia of grade 3 (according to National Cancer Institute Common Terminology Criteria for Adverse Events,version 3.0) occurred in 3 patients each (9%) (1 patient had both) and were managed with dose modification.

Conclusions: Ruxolitinib was generally well tolerated and provided rapid and durable clinical benefits in patients with advanced PV who were refractory or intolerant to hydroxyurea.

Show MeSH
Related in: MedlinePlus